Metabolic profiling identifies Qrich2 as a novel glutamine sensor that regulates microtubule glutamylation and mitochondrial function in mouse sperm.

In our prior investigation, we discerned loss-of-function variants within the gene encoding glutamine-rich protein 2 (QRICH2) in two consanguineous families, leading to various morphological abnormalities in sperm flagella and male infertility. The Qrich2 knockout (KO) in mice also exhibits multiple morphological abnormalities of the flagella (MMAF) phenotype with a significantly decreased sperm motility. However, how ORICH2 regulates the formation of sperm flagella remains unclear. Abnormal glutamylation levels of tubulin cause dysplastic microtubules and flagella, eventually resulting in the decline of sperm motility and male infertility. In the current study, by further analyzing the Qrich2 KO mouse sperm, we found a reduced glutamylation level and instability of tubulin in Qrich2 KO mouse sperm flagella. In addition, we found that the amino acid metabolism was dysregulated in both testes and sperm, leading to the accumulated glutamine (Gln) and reduced glutamate (Glu) concentrations, and disorderly expressed genes responsible for Gln/Glu metabolism. Interestingly, mice fed with diets devoid of Gln/Glu phenocopied the Qrich2 KO mice. Furthermore, we identified several mitochondrial marker proteins that could not be correctly localized in sperm flagella, which might be responsible for the reduced mitochondrial function contributing to the reduced sperm motility in Qrich2 KO mice. Our study reveals a crucial role of a normal Gln/Glu metabolism in maintaining the structural stability of the microtubules in sperm flagella by regulating the glutamylation levels of the tubulin and identifies Qrich2 as a possible novel Gln sensor that regulates microtubule glutamylation and mitochondrial function in mouse sperm.

Multitask prediction models for serous ovarian cancer by preoperative CT image assessments based on radiomics.

Objective: High-grade serous ovarian cancer (HGSOC) has the highest mortality rate among female reproductive system tumors. Accurate preoperative assessment is crucial for treatment planning. This study aims to develop multitask prediction models for HGSOC using radiomics analysis based on preoperative CT images. Methods: This study enrolled 112 patients diagnosed with HGSOC. Laboratory findings, including serum levels of CA125, HE-4, and NLR, were collected. Radiomic features were extracted from manually delineated ROI on CT images by two radiologists. Classification models were developed using selected optimal feature sets to predict R0 resection, lymph node invasion, and distant metastasis status. Model evaluation was conducted by quantifying receiver operating curves (ROC), calculating the area under the curve (AUC), De Long's test. Results: The radiomics models applied to CT images demonstrated superior performance in the testing set compared to the clinical models. The area under the curve (AUC) values for the combined model in predicting R0 resection were 0.913 and 0.881 in the training and testing datasets, respectively. De Long's test indicated significant differences between the combined and clinical models in the testing set (p = 0.003). For predicting lymph node invasion, the AUCs of the combined model were 0.868 and 0.800 in the training and testing datasets, respectively. The results also revealed significant differences between the combined and clinical models in the testing set (p = 0.002). The combined model for predicting distant metastasis achieved AUCs of 0.872 and 0.796 in the training and test datasets, respectively. The combined model displayed excellent agreement between observed and predicted results in predicting R0 resection, while the radiomics model demonstrated better calibration than both the clinical model and combined model in predicting lymph node invasion and distant metastasis. The decision curve analysis (DCA) for predicting R0 resection favored the combined model over both the clinical and radiomics models, whereas for predicting lymph node invasion and distant metastasis, DCA favored the radiomics model over both the clinical model and combined model. Conclusion: The identified radiomics signature holds potential value in preoperatively evaluating the R0, lymph node invasion and distant metastasis in patients with HGSC. The radiomics nomogram demonstrated the incremental value of clinical predictors for surgical outcome and metastasis estimation.

Genome of Laudakia sacra Provides New Insights into High-Altitude Adaptation of Ectotherms.

Anan's rock agama (Laudakia sacra) is a lizard species endemic to the harsh high-altitude environment of the Qinghai-Tibet Plateau, a region characterized by low oxygen tension and high ultraviolet (UV) radiation. To better understand the genetic mechanisms underlying highland adaptation of ectotherms, we assembled a 1.80-Gb L. sacra genome, which contained 284 contigs with an N50 of 20.19 Mb and a BUSCO score of 93.54%. Comparative genomic analysis indicated that mutations in certain genes, including HIF1A, TIE2, and NFAT family members and genes in the respiratory chain, may be common adaptations to hypoxia among high-altitude animals. Compared with lowland reptiles, MLIP showed a convergent mutation in L. sacra and the Tibetan hot-spring snake (Thermophis baileyi), which may affect their hypoxia adaptation. In L. sacra, several genes related to cardiovascular remodeling, erythropoiesis, oxidative phosphorylation, and DNA repair may also be tailored for adaptation to UV radiation and hypoxia. Of note, ERCC6 and MSH2, two genes associated with adaptation to UV radiation in T. baileyi, exhibited L. sacra-specific mutations that may affect peptide function. Thus, this study provides new insights into the potential mechanisms underpinning high-altitude adaptation in ectotherms and reveals certain genetic generalities for animals' survival on the plateau.

The American Paddlefish Genome Provides Novel Insights into Chromosomal Evolution and Bone Mineralization in Early Vertebrates.

Sturgeons and paddlefishes (Acipenseriformes) occupy the basal position of ray-finned fishes, although they have cartilaginous skeletons as in Chondrichthyes. This evolutionary status and their morphological specializations make them a research focus, but their complex genomes (polyploidy and the presence of microchromosomes) bring obstacles and challenges to molecular studies. Here, we generated the first high-quality genome assembly of the American paddlefish (Polyodon spathula) at a chromosome level. Comparative genomic analyses revealed a recent species-specific whole-genome duplication event, and extensive chromosomal changes, including head-to-head fusions of pairs of intact, large ancestral chromosomes within the paddlefish. We also provide an overview of the paddlefish SCPP (secretory calcium-binding phosphoprotein) repertoire that is responsible for tissue mineralization, demonstrating that the earliest flourishing of SCPP members occurred at least before the split between Acipenseriformes and teleosts. In summary, this genome assembly provides a genetic resource for understanding chromosomal evolution in polyploid nonteleost fishes and bone mineralization in early vertebrates.

Diurnal rhythm expression of transcription factor NF-κB subunit p65 in Pelteobagrus vachellii.

The pleiotropic transcription factor nuclear factor-kappa B (NF-κB) has important functions in viral resistance. In the present study, we isolated a p65 subunit of NF-κB cDNA from Pelteobagrus vachellii (termed Pvp65) and characterized it. The full-length p65 cDNA comprised 3651 bp, including a 148-bp 5'-untranslated region (UTR), a 106-bp 3'-UTR, and an open reading frame encoding a 1067-amino acid putative protein. The protein sequence comprised a DNA binding motif, a Rel-homology domain, a Rel protein signature, a putative transcription activation domain, a nuclear localization signal, and a transcription initiation factor IIA domain. The expression of Pvp65 displayed a daily rhythm, with an acrophase at approximately at 15:32 h in the liver, 11:34 h in the spleen, and 16:45 h in the head kidney. In addition, infection with Aeromonas hydrophila caused Pvp65 expression to increase significantly (P < 0.05), and peaking at 12 h post infection in the spleen, at 24 in the head kidney, and at 12 h in the liver. Thus, NF-κB expression might be under light/dark cycle control in P. vachellii, and may be involved in the immune response to A. hydrophila.

Whole Genome Sequencing of Chinese White Dolphin (Sousa chinensis) for High-Throughput Screening of Antihypertensive Peptides.

Chinese white dolphin (Sousa chinensis), also known as the Indo-Pacific humpback dolphin, has been classified as "Vulnerable" on the IUCN Red List of Threatened Species. It is a special cetacean species that lives in tropical and subtropical nearshore waters, with significant differences from other cetaceans. Here, we sequenced and assembled a draft genome of the Chinese white dolphin with a total length of 2.3 Gb and annotation of 18,387 protein-coding genes. Genes from certain expanded families are potentially involved in DNA replication and repairing, suggesting that they may be related to adaptation of this marine mammal to nearshore environments. We also discovered that its historical population had undergone a remarkable bottleneck incident before the Mindel glaciation. In addition, a comparative genomic survey on antihypertensive peptides (AHTPs) among five representative mammals with various residential habitats (such as remarkable differences in exogenous ion concentrations and sea depth) revealed that these small bioactive peptides were highly conserved among these examined mammals, and they had the most abundant hits in collagen subunit proteins, especially for two putative AHTP peptides Gly-Leu-Pro (GLP) and Leu-Gly-Pro (LGP). Our genome assembly will be a valuable resource for further genetic researches on adaptive ecology and conservation biology of cetaceans, and for in-depth investigations into bioactive peptides in aquatic and terrestrial mammals for development of peptide-based drugs to treat various human cardiovascular diseases.

High Throughput Identification of Antihypertensive Peptides from Fish Proteome Datasets.

Antihypertensive peptides (AHTPs) are a group of small peptides with the main role to block key enzymes or receptors in the angiotensin genesis pathway. A great number of AHTPs have been isolated or digested from natural food resources; however, comprehensive studies on comparisons of AHTPs in various species from the perspective of big data are rare. Here, we established a simplified local AHTP database, and performed in situ mapping for high throughput identification of AHTPs with high antihypertensive activity from high-quality whole proteome datasets of 18 fish species. In the 35 identified AHTPs with reported high activity, we observed that Gly-Leu-Pro, Leu-Pro-Gly, and Val-Ser-Val are the major components of fish proteins, and AHTP hit numbers in various species demonstrated a similar distributing pattern. Interestingly, Atlantic salmon (Salmo salar) is in possession of far more abundant AHTPs compared with other fish species. In addition, collagen subunit protein is the largest group with more matching AHTPs. Further exploration of two collagen subunits (col4a5 and col8a1) in more fish species suggested that the hit pattern of these conserved proteins among teleost is almost the same, and their phylogeny is consistent with the evolution of these fish species. In summary, our present study provides basic information for the relationship of AHTPs with fish proteins, which sheds light on rapid discovery of marine drugs or food additives from fish protein hydrolysates to alleviate hypertension.

DNA barcoding and the identification of tree frogs (Amphibia: Anura: Rhacophoridae).

The DNA barcoding gene COI (cytochrome c oxidase subunit I) effectively identifies many species. Herein, we barcoded 172 individuals from 37 species belonging to nine genera in Rhacophoridae to test if the gene serves equally well to identify species of tree frogs. Phenetic neighbor joining and phylogenetic Bayesian inference were used to construct phylogenetic trees, which resolved all nine genera as monophyletic taxa except for Rhacophorus, two new matrilines for Liuixalus, and Polypedates leucomystax species complex. Intraspecific genetic distances ranged from 0.000 to 0.119 and interspecific genetic distances ranged from 0.015 to 0.334. Within Rhacophorus and Kurixalus, the intra- and interspecific genetic distances did not reveal an obvious barcode gap. Notwithstanding, we found that COI sequences unambiguously identified rhacophorid species and helped to discover likely new cryptic species via the synthesis of genealogical relationships and divergence patterns. Our results supported that COI is an effective DNA barcoding marker for Rhacophoridae.